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PubMed2001

[Predictive value of prostate specific antigen density in the detection of prostate cancer in patients with elevated prostate specific antigen levels and normal digital rectal findings or stage A prostate cancer].

We compared the usefulness of PSA and PSA density (PSAD) in diagnosing prostate cancer in 102 men who had a PSA value higher than 4.0 ng/ml and normal digital rectal examination and who had undergone transrectal ultrasonography-guided systematic sextant biopsies of the prostate between August 1996 and October 1999. In addition, for a group of 53 patients who underwent retropubic simple prostatectomy, PSA, PSAD and PSA transition zone (PSA-TZ) examination results for those with stage A prostate cancer were compared with the results for those with benign prostatic hyperplasia (BPH). Of the former 102 men, 20 (19.6%) had prostate cancer. There was no significant difference in mean PSA level between patients with negative and those with positive biopsy results (mean 9.3 and 11.8, respectively, p = 0.295), but the mean PSAD of patients with positive biopsy results was significantly higher than that of those with negative results (mean 0.55 and 0.29, respectively, p = 0.0007). Of the 53 men who underwent retropubic simple prostatectomy, 10 (18.9%) were diagnosed with stage A prostate cancer. There was no significant difference in mean PSA, PSAD and PSA-TZ examination results between patients with BPH and those with stage A prostate cancer. For all 102 patients and for 71 patients with PSA levels of 4.1-10.0 ng/ml, a PSAD cutoff value of 0.1 reduced the number of biopsies 15.7% (16 of 102 cases), and 22.5% (16 of 71 cases), respectively. These results suggest that by measurement of PSAD some patients with benign disease could be spared a biopsy which would have been performed based on PSA results alone.

Aged↗
PubMed2003

Polarity of prostate specific membrane antigen, prostate stem cell antigen, and prostate specific antigen in prostate tissue and in a cultured epithelial cell line.

BACKGROUND: Madin-Darby canine kidney (MDCK) cells are immortalized epithelial cells that have been used extensively as a model system to study intracellular molecular trafficking, polarized expression, and secretion of proteins in various epithelia. In order to determine if MDCK cells might serve as a model to study molecular events within prostate epithelial cells, we have evaluated the polarized distribution of three prostate restricted proteins, PSMA, PSCA, and PSA, in situ, and in MDCK cells. METHODS: Using immunofluorescence, confocal microscopy, cell surface biotinylation, antibody internalization, and biochemical assays we evaluated surface expression and secretion of three prostate restricted proteins expressed in MDCK cells. We compared these patterns of expression to results observed within prostatic epithelium. RESULTS: We demonstrate that PSMA is localized primarily to the apical plasma membrane in both the prostatic epithelium and transfected MDCK cells, whereas PSCA is expressed in a non-polarized fashion. We also show that PSA is secreted predominantly from the apical surface of transfected MDCK cells, consistent with in vivo observations. CONCLUSIONS: Similar patterns of localization among MDCK and prostatic epithelial cells suggest that the mechanisms of polarized sorting within these cell types are conserved. Thus, MDCK cells offer a useful model system to study mechanisms of targeting of these proteins within the prostate.

Animals↗
PubMed2004

Differentiation of benign prostatic hyperplasia from prostate cancer using prostate specific antigen dynamic profile after transrectal prostate biopsy.

PURPOSE: Serum prostate specific antigen (PSA) level is increased after needle biopsy (Bx) of the prostate. This study tested the hypothesis that the prostate harboring malignant lesions demonstrates less leakage of PSA after prostate biopsy and this phenomenon can be helpful in discriminating benign from cancer diagnosis. MATERIALS AND METHODS: This prospective study was divided into 3 separate phases. Sextant prostate biopsy was done with transrectal ultrasound guidance, and the change and PSA values after biopsy were evaluated. Phases 1 and 2 had 20 and 41 patients, respectively. PSA dynamic profiles were plotted. We defined the most appropriate timing for blood sampling and the cutoff value of the PSA ratio (post-Bx total PSA-to-pre-Bx total PSA) to be applied for further assessment. Phase 3 recruited 97 cases, of which 66 satisfied the end point criteria in which a diagnosis such as malignancy, or 3 successive benign biopsies or benign transurethral resection of prostate was obtained. RESULTS: From phases 1 and 2 the cutoff value for the PSA ratio was 2.0, and the timing of blood sampling was 60 minutes after the biopsy. In phase 3 of those whose PSA ratio was less than 2.0, 92.6% (25) had cancer. For those whose PSA ratio was greater than 2.0, 82.1% (32) were benign. Of the 4 cases with a PSA ratio less than 2.0 and an initial benign biopsy, 3 (75%) were proven to have cancer later. CONCLUSIONS: Evaluating the 1-hour PSA ratio might be helpful for clinicians to select the high risk patients who might have cancer in the prostate. Repeat biopsy should be suggested for cases with a smaller PSA ratio in spite of initial benign results.

Aged↗
PubMed2005

Elevation of dipeptidylpeptidase iv activities in the prostate peripheral zone and prostatic secretions of men with prostate cancer: possible prostate cancer disease marker.

PURPOSE: Dipeptidylpeptidase IV (DPIV) is a multifunctional type II plasma membrane glycoprotein with serine-type exopeptidase activity that is secreted by the prostate and increased in prostate cancer. We determined whether changes in DPIV activities in prostatic tissue zones and expressed secretions were associated with the presence of cancer. MATERIALS AND METHODS: Expressed prostatic secretion (EPS), and biopsy of the transition (TZ) and peripheral (PZ) zones were collected from men undergoing ultrasound guided prostate biopsy. DPIV activities were measured by glypro-p-nitroanalide hydrolysis. RESULTS: DPIV activities were significantly higher in TZ than in PZ tissues in men with no evidence of malignancy. However, activities in EPS were negatively associated with TZ volume and positively associated with PZ volume. Mean and median DPIV activities in EPS from men with biopsy determined cancer were significantly higher than in men with no evidence of malignancy. DPIV activities in TZ and PZ biopsies were higher in men with cancer but most markedly in the PZ. CONCLUSIONS: These data indicate that secreted DPIV originates from the TZ and PZ. Increased DPIV activities in cancer are strongly associated with the PZ, which is the zone most commonly involved with cancer. Measuring DPIV levels in expressed EPS or post-digital rectal prostate examination urine may be useful for evaluating men for prostate cancer.

Adenosine Deaminase↗
PubMed1993

Comparison of prostate secretory protein with prostate specific antigen and prostatic acid phosphatase as a serum biomarker for diagnosis and monitoring patients with prostate carcinoma.

Serum prostate secretory protein (PSP) levels were measured in 49 patients with benign prostatic hyperplasia (BPH), 144 patients with various stages of prostatic carcinoma (CaP), and 82 CaP patients who were followed serially. PSP values were compared with serum levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). In the BPH group, PSP was elevated (> 10 ng/ml) in 41% of patients, whereas PSA (> 4 ng/ml) and PAP (> 3.3 ng/ml) were elevated in 39% and 23% of the cases, respectively. PSP levels were elevated in 48% of the CaP pretreatment specimens, compared to 79% for PSA and 40% for PAP. PSP levels in cancer patients who had intracapsular disease were about two to three times higher than those observed for PAP. PSP was found to be the only marker elevated in eight (6%) pretreatment CaP patient serum specimens, while PAP was never found to be elevated when PSA was normal. PSP serum concentrations correlated with the clinical course of the disease in 79% of patients, compared with 90% for PSA and 66% for PAP. In certain patients, monitored over time, disease correlation was reflected in serum values with only a single biomarker, i.e., 1% with PAP, 8% with PSP, and 10% with PSA. This study has shown that PSP is a less sensitive serum biomarker than PSA, but more sensitive than PAP for detection and monitoring the early stages of prostate cancer. This suggests that PSP as a biomarker may be a useful adjunct for the management of a subpopulation of low-stage and -grade CaP.

Acid Phosphatase↗
PubMed2001

Should prostate-specific antigen or prostate-specific antigen density be used as the determining factor when deciding which prostates should undergo biopsy during prostate ultrasound.

Prostate ultrasound has been accepted as the appropriate tool for prostate biopsy guidance to determine the presence of prostate cancer if the prostate-specific antigen (PSA) level is not normal. Prostate-specific antigen density (PSAD) has been used to determine if an increased PSA level may be because of benign enlargement of the gland or possible presence of cancer. The specific "cutoff" for PSA and PSAD to delineate which patients are at highest risk has been controversial. We attempted to assess which PSA level or PSAD level should be used. A retrospective analysis of 600 consecutive men, referred for prostate ultrasound and possible biopsy because of an abnormal DRE result or increased PSA level was undertaken. All had prostate volume determined by biplanar endorectal ultrasound. One hundred sixty-six men had cancer confirmed by biopsy. This latter group was further analyzed and was divided into PSA <4.0, PSA 4 to 10, or PSA >10.0 ng/ml. Groups were divided according to those with PSAD <0.10, <0.12, and <0.15 ng/ml. Correlation with Gleason grade of the tumor was made. Of the 166 men with cancer, 15 had PSA levels <4 ng/ml (all palpable), and 81 had PSA levels between 4.0 and 10.0 ng/ml (48 were not palpable by digital rectal examination [DRE]). There were 38 (22.8%) of 166 men with cancer who had a PSAD <0.15. Using the Gleason scoring system, 30 of 38 men had mid-grade or high-grade cancers. Twenty-one (12.6%) of 166 men with cancer had a PSAD <0.12. Of these, 17 of 21 men had mid-grade or high-grade cancers. Fifteen (9.0%) of 166 men with cancer had a PSAD <0.10. Of these, 13 of 15 had mid-grade or high-grade cancer. If the PSA level is more than 4.0 ng/ml, even if no palpable lesion is discerned by DRE, suspicion for the presence of cancer should be raised. The use of PSAD threshold of 0.15 is not inclusive enough to identify clinically important cancer, and it should not be used. Our data demonstrate that 7.9% of men with cancer had a PSAD <0.15 and mid-grade or high-grade, i.e., clinically important, cancer. Although more negative biopsy results will be obtained, we recommend the use of a lower PSAD "cutoff" than the literature has suggested. We recommend that those men with PSA levels more than 4 ng/ml and a PSAD higher than 0.10 should undergo a prostate biopsy to detect clinically important cancer.

Journal Article↗
PubMed1992

Volume of normal prostate, of prostate cancer, and of benign prostatic hyperplasia: are correlations with prostate specific antigen clinically useful?

This retrospective study correlated prostate volume, determined by transrectal ultrasonography, with serum prostate specific antigen (PSA), by Deming regression analysis, in patients with confirmed benign prostatic hyperplasia (BPH) and patients with non-metastatic (M0) or metastatic (M1) prostate cancer. In BPH, a highly significant correlation was found between log10[PSA] and prostate volume. When this PSA/volume regression pattern for BPH was used as a reference standard, all 17 patients with M1 prostate cancer and 83% of the 23 patients with M0 disease were discriminated from BPH.

Aged↗
PubMed1997

Significance of examination of prostate-specific antigen and prostate-specific antigen density in patients with prostatic hyperplasia and prostate cancer.

Authors investigated PSA concentration and preoperative prostate volume in 113 histologically proved BPH and 31 prostatic cancer patients. PSA concentration was measured with the Hybritech kit, the prostate volume by ultrasound with the help of an ellipse and calculated by computer. There was no correlation between the age of patients and volume of the prostate, whereas a correlation was proved between marker concentration and prostate volume (p < 0.0001). The difference obtained by the correlation of the prostate volume and the PSA concentration ratio between the BPH and 31 tumorous patients (PSA density) was highly significant (0.143 vs. 0.699, p < 0.001). The use of PSAD further improves the diagnostic value of PSA.

Age Factors↗
PubMed1993

A comparative study on expression of prostatic inhibin peptide, prostate acid phosphatase and prostate specific antigen in androgen independent human and rat prostate carcinoma cell lines.

Prostatic inhibin peptide (PIP), consisting of 94 amino-acid residues is synthesized and secreted by the prostate gland. Previous studies on immunohistochemical localization of PIP in primary prostatic tumor and their metastasis, have documented the value of this peptide as a tumor marker for diagnosis of prostate cancer (PCa). The present study was undertaken to compare the expression of PIP with that of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in androgen independent human PCa cell lines (PC-3, DU-145 and TSU-Prl) by immunoperoxidase technique. The results of the study indicated that the staining for PIP was more intense than that of PSA and PAP. The PSA staining was either weakly positive (PC-3) or totally absent (TSU-Prl and DU-145) while PAP staining was intense in PC-3 and moderate in the other two human cell lines. The intense staining observed for PIP in all of the androgen independent cell lines suggests that the synthesis and secretion of PIP is not primarily dependent on androgens. Furthermore, expression of these markers in Dunning rat cultured adenocarcinoma cell lines and tumors were studied. Positive staining for all three human tumor associated antigens (PIP, PSA and PAP) cross-reacting with the Dunning rat PCa cell lines and the tumors, suggest the suitability of this model for preclinical screening of various therapeutic agents.

Acid Phosphatase↗
PubMed2004

Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues: implications for prostate carcinogenesis and progression of prostate cancer.

OBJECTIVE: Prostate stem cell antigen (PSCA) is a recently defined homolog of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. The objective of the present study was to examine the expression status of PSCA protein and mRNA in clinical specimens of human prostate cancer (PCa) and to validate it as a potential molecular target for diagnosis and treatment of PCa. METHODS: Immunohistochemical (IHC) and in situ hybridization (ISH) analyses of PSCA expression were simultaneously performed on paraffin-embedded sections of 20 benign prostatic hyperplasia (BPH), 20 prostatic intraepithelial neoplasm (PIN) and 48 prostate cancer (PCa) tissues, including 9 androgen-independent prostate cancers. The level of PSCA expression was semiquantitatively scored by assessing both the percentage and intensity of PSCA-positive staining cells in the specimens. We then compared the PSCA expression between BPH, PIN and PCa tissues and analyzed the correlations of PSCA expression level with pathological grade, clinical stage and progression to androgen-independence in PCa. RESULTS: In BPH and low grade PIN, PSCA protein and mRNA staining were weak or negative and less intense and uniform than that observed in high grade PIN (HGPIN) and PCa. Moderate to strong PSCA protein and mRNA expression were noted in 8 of 11 (72.7%) HGPIN and in 40 of 48 (83.4%) PCa specimens examined by IHC and ISH analyses, and their statistical significance was compared with BPH (20%) and low-grade PIN (22.2%) specimens (P < 0.05). The expression level of PSCA increased with a higher Gleason grade, advanced stage and progression to androgen-independence (P < 0.05). In addition, IHC and ISH staining revealed a high degree of correlation between PSCA protein and mRNA overexpression. CONCLUSIONS: Our data demonstrate that PSCA as a new cell surface marker is overexpressed in a majority of cases of human PCa. PSCA expression correlates positively with adverse tumor characteristics, such as increasing pathological grade (poor cell differentiation), worsening clinical stage and androgen-independence and speculatively with prostate carcinogenesis. PSCA may possess prognostic utility and may be a promising molecular target for diagnosis and treatment of PCa.

Aged↗
PubMed1994

Prostate inhibin peptide (PIP) in prostate cancer: a comparative immunohistochemical study with prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP).

Prostate inhibin peptide (PIP) is a polypeptide synthesized by the prostate gland that is involved in prostatic growth and differentiation. The objective of this study was to evaluate PIP as an immunocytochemical marker for prostatic adenocarcinoma (PCA) by comparing it with PSA and PAP. A total of 71 cases of primary PCA and 5 cases of metastatic PCA were studied. Primary tumors were specially selected to include a disproportionate number of high-grade tumors. The distribution of cases by Gleason score was 2-5, 14 cases; 6-7, 24 cases; and 8-10, 33 cases. Four metastases were to bone (decalcified tissue) and one to soft tissue. All 71 cases of primary PCA stained positively for the three antibodies tested, with none demonstrating obvious superiority, although individual case variability was seen. In one bone metastasis, staining for PSA was negative, with both PAP and PIP giving positive results. All non-prostatic carcinomas tested were negative. These results indicate that PIP is as sensitive and specific an immunohistochemical marker as PSA and PAP in untreated prostate adenocarcinomas. Further, the androgen-independent nature of PIP may give it an advantage over PSA/PAP in tumors exposed to androgen ablating agents.

Acid Phosphatase↗
PubMed2002

Percentage of core lengths involved with prostate cancer: does it add to the percentage of positive prostate biopsies in predicting postoperative prostate-specific antigen outcome for men with intermediate-risk prostate cancer?

OBJECTIVES: To evaluate whether the percentage of core lengths involved with prostate cancer added clinically significant information concerning the time to postoperative prostate-specific antigen (PSA) failure in the intermediate-risk patient beyond what is provided by the percentage of positive biopsies. METHODS: Cox regression multivariable analysis was performed to compare the ability of the two measurements of biopsy cancer volume to predict the time to PSA failure from a series of 184 surgically treated intermediate-risk patients. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and comparisons were made using the log-rank test. RESULTS: Both the percentage of core lengths involved with prostate cancer (P = 0.01) and the percentage of positive biopsies (P = 0.002) were significant predictors of the time to PSA failure on univariable analysis. The 4-year PSA outcome was 83% versus 47% (P = 0.0008) and 83% versus 53% (P = 0.007) for the percentage of positive biopsies stratified by 50% or less versus greater than 50% and the percentage of core lengths involved with prostate cancer stratified by 25% or less versus greater than 25%, respectively. However, only the percentage of positive biopsies remained significant (P = 0.03) on multivariable analysis. CONCLUSIONS: The percentage of core lengths involved with prostate cancer did not provide additional clinically relevant information to the percentage of positive biopsies for patients with intermediate-risk prostate cancer. Therefore, the routine measurement of core involvement may not be necessary in this patient population.

Analysis of Variance↗
PubMed2004

Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues and its potential role in prostate carcinogenesis and progression of prostate cancer.

BACKGROUND: Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. The purpose of the present study was to examine the expression status of PSCA protein and mRNA in clinical specimens of human prostate cancer (Pca) and to validate it as a potential molecular target for diagnosis and treatment of Pca. MATERIALS AND METHODS: Immunohistochemical (IHC) and in situ hybridization (ISH) analyses of PSCA expression were simultaneously performed on paraffin-embedded sections from 20 benign prostatic hyperplasia (BPH), 20 prostatic intraepithelial neoplasm (PIN) and 48 prostate cancer (Pca) tissues, including 9 androgen-independent prostate cancers. The level of PSCA expression was semiquantitatively scored by assessing both the percentage and intensity of PSCA-positive staining cells in the specimens. Then compared PSCA expression between BPH, PIN and Pca tissues and analysed the correlations of PSCA expression level with pathological grade, clinical stage and progression to androgen-independence in Pca. RESULTS: In BPH and low grade PIN, PSCA protein and mRNA staining were weak or negative and less intense and uniform than that seen in HGPIN and Pca. There were moderate to strong PSCA protein and mRNA expression in 8 of 11 (72.7%) HGPIN and in 40 of 48 (83.4%) Pca specimens examined by IHC and ISH analyses, with statistical significance compared with BPH (20%) and low grade PIN (22.2%) samples (p < 0.05, respectively). The expression level of PSCA increased with high Gleason grade, advanced stage and progression to androgen-independence (p < 0.05, respectively). In addition, IHC and ISH staining showed a high degree of correlation between PSCA protein and mRNA overexpression. CONCLUSIONS: Our data demonstrate that PSCA as a new cell surface marker is overexpressed by a majority of human Pca. PSCA expression correlates positively with adverse tumor characteristics, such as increasing pathological grade (poor cell differentiation), worsening clinical stage and androgen-independence, and speculatively with prostate carcinogenesis. PSCA protein overexpression results from upregulated transcription of PSCA mRNA. PSCA may have prognostic utility and may be a promising molecular target for diagnosis and treatment of Pca.

Duplicate Publication↗
PubMed2002

Reverse transcription-polymerase chain reaction detection of prostate-specific antigen, prostate-specific membrane antigen, and prostate stem cell antigen in one milliliter of peripheral blood: value for the staging of prostate cancer.

PURPOSE: There have been several studies on the presence of circulating tumor cells in the peripheral blood of patients with malignant tumors including prostate cancer (PCa) using reverse transcription-PCR (RT-PCR). One of the aims of these studies was to obtain high sensitivity that would enable early-stage diagnosis. However, they varied in their detection rates, and the methods were rather complicated. We have improved the RT-PCR assay combining three prostate-associated molecules, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA) to reveal patients with poor prognosis. EXPERIMENTAL DESIGN: Peripheral blood samples were obtained from 129 patients including 58 cases of PCa and 71 cases of nonmalignant disorders. Total RNA was extracted from 1 ml of whole blood using a commercially available kit. RESULTS: The sensitivity of PSA-, PSMA-, and PSCA-nested RT-PCR was verified with positive signals of a single LNCaP cell in 1 ml of female blood sample. PSA-, PSMA-, and PSCA-mRNA were detected in 7 (12.1%), 12 (20.7%), and 8 (13.8%) PCa, and in 1, 2, and 0 samples in nonmalignant disorders, respectively. Among 58 PCa patients, each PCR indicated the prognostic value in the hierarchy of PSCA>PSA>PSMA RT-PCR, and extraprostatic cases with positive PSCA PCR indicated lower disease-progression-free survival than those with negative PSCA PCR. CONCLUSIONS: The present findings suggest that PSCA PCR would be most promising for the molecular staging of PCa. The present RT-PCR is a highly cost-effective and rapid procedure, enabling the molecular staging of PCa with RT-PCR as a diagnostic routine.

Antigens, Neoplasm↗
PubMed1998

Allelic imbalance in familial and sporadic prostate cancer at the putative human prostate cancer susceptibility locus, HPC1. CRC/BPG UK Familial Prostate Cancer Study Collaborators. Cancer Research Campaign/British Prostate Group.

A recent report has provided strong evidence for a major prostate cancer susceptibility locus (HPC1) on chromosome 1q24-25 (Smith et al, 1996). Most inherited cancer susceptibility genes function as tumour-suppressor genes (TSGs). Allelic loss or imbalance in tumour tissue is often the hallmark of a TSG. Studies of allelic loss have not previously implicated the chromosomal region 1q24-25 in prostate cancer. However, analysis of tumour DNA from cases in prostate cancer families has not been reported. In this study, we have evaluated DNA from tissue obtained from small families [3-5 affected members (n = 17)], sibling pairs (n = 15) and sporadic (n = 40) prostate tumours using the three markers from Smith et al (1996) that defined the maximum multipoint linkage lod score. Although widely spaced (12-50 cM), each marker showed evidence of allelic imbalance in only approximately 7.5% of informative tumours. There was no difference between the familial and sporadic cases. We conclude that the incidence of allelic imbalance at HPC1 is low in both sporadic tumours and small prostate cancer families. In this group of patients, HPC1 is unlikely to be acting as a TSG in the development of prostate cancer.

Aged↗
PubMed1995

[Results of studies of prostate-specific antigen and prostate-specific antigen density in patients with prostatic hypertrophy and prostatic cancer].

The authors investigated the PSA concentration and the preoperative prostate volume of 113 histologically proved BPH and 31 prostate cancer patients. There was no correlation between the age of the patients and the volume of the prostate. Whereas, correlation was proved between the marker concentration and the prostate volume (p < 0.0001). The prostate volume and the PSA concentration ratio correlated between the BPH and tumorous patients (PSA density). The difference was highly significant (p < 0.001). The use of PSAD improves further the diagnostical value of PSA.

Aged↗
PubMed2001

Disappearance of well-differentiated carcinoma of the prostate: effect of transurethral resection of the prostate, prostate-specific antigen, and prostate biopsy.

OBJECTIVES: To characterize the effect of prostate-specific antigen (PSA) and transurethral resection of the prostate (TURP) on the rate of diagnosis of well-differentiated (WD) prostate cancer (PCa) and PCa mortality. METHODS: All cases of PCa and rates of TURP at both Wilford Hall and Brooke Army Medical Centers between 1984 and 1995 were reviewed. Tumor grade was compared between prostate needle biopsy and TURP. The pattern of diagnosis was analyzed annually and for two time periods: pre-PSA (1984 to 1988) and post-PSA (1989 to 1995). RESULTS: The number of WD tumors fell by 50% over the period of study and was caused by a fall in number of TURPs as well as in WD tumors detected by TURP. PSA for early detection of PCa began in 1988, and within 5 years a more than 50% fall in the rate of metastatic disease was witnessed. These two events (PSA screening and fall in TURPs) led to an increase from 57% to 92% of tumors that were both clinically significant and potentially curable. CONCLUSIONS: These data help explain the fall in the rate of diagnosis of WD PCa. The resultant increase in the diagnosis of moderately and poorly differentiated PCa, coupled with the dramatic fall in the rate of diagnosis of metastatic PCa, may explain the reports of a fall in PCa mortality. If this observation is replicated in other populations, it may provide further impetus for a stronger recommendation for early detection with PSA and digital rectal examination.

Biomarkers, Tumor↗